New prognostic scoring system for mortality in idiopathic pulmonary fibrosis by modifying the gender, age, and physiology model with desaturation during the six-minute walk test.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry. Materials and methods: This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model. Results: Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38-3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60-4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p < 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality. Conclusion: The GAP6 model adding nadir SpO2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system.

Clinical Experiences of High-Risk Pulmonary Thromboembolism Receiving Extracorporeal Membrane Oxygenation in Single Institution.

BACKGROUND: The main cause of death in pulmonary embolism (PE) is right-heart failure due to acute pressure overload. In this sense, extracorporeal membrane oxygenation (ECMO) might be useful in maintaining hemodynamic stability and improving organ perfusion. Some previous studies have reported ECMO as a bridge to reperfusion therapy of PE. However, little is known about the patients that benefit from ECMO. METHODS: Patients who underwent ECMO due to pulmonary thromboembolism at a single university-affiliated hospital between January 2010 and December 2018 were retrospectively reviewed. RESULTS: During the study period, nine patients received ECMO in high-risk PE. The median age of the patients was 60 years (range, 22-76 years), and six (66.7%) were male. All nine patients had cardiac arrests, of which three occurred outside the hospital. All the patients received mechanical support with veno-arterial ECMO, and the median ECMO duration was 1.1 days (range, 0.2-14.0 days). ECMO with anticoagulation alone was performed in six (66.7%), and ECMO with reperfusion therapy was done in three (33.3%). The 30-day mortality rate was 77.8%. The median time taken from the first cardiac arrest to initiation of ECMO was 31 minutes (range, 30-32 minutes) in survivors (n=2) and 65 minutes (range, 33-482 minutes) in non-survivors (n=7). CONCLUSION: High-risk PE with cardiac arrest has a high mortality rate despite aggressive management with ECMO and reperfusion therapy. Early decision to start ECMO and its rapid initiation might help save those with cardiac arrest in high-risk PE.

Post-Coronavirus Disease 2019 Pulmonary Fibrosis: Wait or Needs Intervention.

Coronavirus disease 2019 (COVID-19) has become a major health burden worldwide, with over 450 million confirmed cases and 6 million deaths. Although the acute phase of COVID-19 management has been established, there is still a long way to go to evaluate the long-term clinical course or manage complications due to the relatively short outbreak of the virus. Pulmonary fibrosis is one of the most common respiratory complications associated with COVID-19. Scarring throughout the lungs after viral or bacterial pulmonary infection have been commonly observed, but the prevalence of post- COVID-19 pulmonary fibrosis is rapidly increasing. However, there is limited information available about post-COVID-19 pulmonary fibrosis, and there is also a lack of consensus on what condition should be defined as post-COVID-19 pulmonary fibrosis. During a relatively short follow-up period of approximately 1 year, lesions considered related to pulmonary fibrosis often showed gradual improvement; therefore, it is questionable at what time point fibrosis should be evaluated. In this review, we investigated the epidemiology, risk factors, pathogenesis, and management of post-COVID-19 pulmonary fibrosis.

Clinical Features, Diagnosis, Management, and Outcomes of Idiopathic Pulmonary Fibrosis in Korea: Analysis of the Korea IPF Cohort (KICO) Registry.

BACKGROUND: The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients. METHODS: Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015. RESULTS: A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-agephysiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality. CONCLUSION: In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

Clinical outcomes of dose modification during pirfenidone treatment for IPF: A nationwide post-marketing surveillance study.

Background: Pirfenidone, an antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), often requires dose reduction owing to adverse events. In this study, we evaluated if pirfenidone's reduced dose has any impact on clinical outcomes in patients with IPF. Methods: We used the data of a prospective post-marketing study of pirfenidone conducted at 10 hospitals in South Korea from 2014 to 2017. Dose reduction was defined when the pirfenidone dose was temporarily or permanently reduced to manage adverse events or when the treatment dose failed to reach the standard dose. Study patients were classified based on the most frequently administered dose during 48-week follow-up-1800 mg, 1,200 mg, and <1,200 mg/days. The following clinical outcomes were compared between the groups: death, hospitalization, acute exacerbation, pulmonary function decline, and changes in severity of dyspnea and cough. Results: The median follow-up duration in all 143 patients was 11 months. During the study period, 70.6% experienced at least one dose reduction. Patients treated with standard-dose pirfenidone tended to be young and had the lowest diffusing capacity. Pulmonary function changes did not differ depending on the pirfenidone dose. The three groups were not significantly different in terms of the proportion of death, hospitalization, and acute exacerbation. The symptom changes were also similar between the groups. Conclusion: Reduced doses did not negatively impact clinical outcomes compared with the standard-dose pirfenidone in patients with IPF. Dose reduction may be a useful method to manage adverse events while maintaining therapeutic efficacy.

Therapy-related myeloid leukemia during erlotinib treatment in a non-small cell lung cancer patient: A case report.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are tolerable drugs used for patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). Serious adverse reactions are uncommon compared with cytotoxic drugs. CASE SUMMARY: A 52-year-old man presented with general weakness and cytopenia. He had been taking erlotinib for 11 mo to treat NSCLC. The pathological diagnosis from the right upper lobe mass was adenocarcinoma with an EGFR mutation in exon 21 (L858R). He had previously received paclitaxel/carboplatin, gemcitabin/ vinorelbine chemotherapy, stereotactic radiosurgery for brain metastasis, and whole-brain radiotherapy as treatment for NSCLC. We diagnosed the patient with acute myeloid leukemia (AML). During the induction and consolidation chemotherapy for AML, the erlotinib was discontinued. When complete remission of the AML was achieved, since the lung masses were increased, pemetrexed/ cisplatin for the NSCLC was initiated. After two cycles of chemotherapy, the cytopenia was prolonged. AML relapse occurred with the same karyotype. CONCLUSION: Therapy-related acute myeloid neoplasm (t-MN) is a rare but fatal late complication. Although a patient may be taking EGFR-TKIs, the possibility of t-MN should be considered. Further studies are needed to determine whether EGFR-TKI usage is a predisposing factor for t-MN.

Longitudinal Changes in Clinical Features, Management, and Outcomes of Idiopathic Pulmonary Fibrosis. A Nationwide Cohort Study.

Rationale: In recent decades, diagnosis and treatment recommendations for idiopathic pulmonary fibrosis (IPF) have changed. In Korea, the average life expectancy has increased, unmet healthcare needs have been reduced, and the number of computed tomographic examinations performed has nearly doubled. The Korean Interstitial Lung Disease Study Group conducted a nationwide cohort study for idiopathic interstitial pneumonia, including IPF, and established a registry for IPF.Objectives: Using study data collected by the study group, this study aimed to evaluate longitudinal changes in clinical features, diagnosis, treatment, and mortality and analyze the extent to which changes in medication usage affected IPF-associated mortality.Methods: The study population included newly diagnosed patients with IPF from a cohort study (January 2002 to September 2008, n = 1,839, 2008 group) and prospective registry (January 2012 to August 2018, n = 1,345, 2018 group). Survival curves were estimated using the Kaplan-Meier method, and Cox regression models were used to identify mortality-associated risk factors in each group.Results: The 2018 group was younger, had fewer symptoms, had less honeycombing, underwent more serologic autoimmune marker and pulmonary function tests, had higher oxygen partial pressure and lower carbon dioxide partial pressure values, was less frequently diagnosed by surgical biopsy, and had better survival than the 2008 group. Steroid use and conservative care declined, whereas N-acetylcysteine use increased in this group. Antifibrotic agents were used in only the 2018 group. In the 2008 group, N-acetylcysteine was associated with lower mortality, whereas conservative care was associated with higher mortality. In the 2018 group, the use of antifibrotic agents was associated with lower mortality, and steroid use was associated with higher mortality. The survival rates in the 2008 and 2018 non-antifibrotic agent subgroups were similar.Conclusions: This study analyzed national IPF cohort data spanning 17 years. In clinical practice, the IPF diagnosis was made earlier, steroid and immunosuppressive agent use was reduced, and antifibrotic agents were administered. The survival of patients with IPF has improved over the decades, and antifibrotic use was consistently associated with improved survival.Clinical trial registered with clinicaltrials.gov (NCT04160715).

Safety and Efficacy of Pirfenidone in Advanced Idiopathic Pulmonary Fibrosis: A Nationwide Post-Marketing Surveillance Study in Korean Patients.

AIM: The efficacy and safety of pirfenidone have been previously demonstrated in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, the effect of pirfenidone in patients with advanced IPF remains unclear. Here, we investigated the effects of pirfenidone against advanced IPF in a real-world setting. METHODS: A prospective nationwide post-marketing study was conducted on 258 patients from 10 Korean institutions. Patients with a predicted forced vital capacity (FVC) less than 50% or a diffusing capacity of the lung for carbon monoxide (DLco) less than 35% at baseline were classified as the advanced IPF group. RESULTS: Of 219 patients included in the analysis, the majority were male (76.3%); the mean age was 67.3 years, and the advanced group accounted for 17.8% of the patients. The median treatment duration was 298 days. Among the subjects, 86.3% experienced adverse events (AEs), of which a decreased appetite (32.4%) and a photosensitivity reaction (13.7%) were the most frequent. The incidence of AEs was similar between the advanced and non-advanced groups (92.3% vs. 85.0%, respectively; p = 0.229). Although the overall discontinuation rate was higher in the advanced group than in the non-advanced group (74.4% vs. 50.0%, respectively; p = 0.006), the percentages of the patients who discontinued treatment as a result of AEs were similar in both groups (20.5% vs. 23.3%, respectively; p = 0.704). In all patients, the rates of decline in the predicted FVC and DLco over 48 weeks were - 4.3 ± 1.3% and - 4.4 ± 1.7%, respectively. There was no between-group difference in the rate of lung function decline. CONCLUSIONS: Pirfenidone used for the treatment of patients with IPF in a real-world setting was well tolerated, with an acceptable safety profile and a consistent therapeutic effect, regardless of the disease severity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03761082; the trial was retrospectively registered on December 3, 2018.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 2. Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

Association of Genetic Variants of NLRP4 with Exacerbation of Asthma: The Effect of Smoking.

Asthma exacerbation is induced by the interaction of genes and environmental factors such as cigarette smoke. NLRP4 counteracts the activity of the inflammasome, which is responsible for asthma exacerbation. In this study, we analyzed the association of single-nucleotide polymorphisms of NLRP4 with the annual rate of exacerbation and evaluated the additive effect of smoking in 1454 asthmatics. Asthmatics possessing the minor allele of rs1696718G > A had more frequent exacerbation episodes than those homozygous for the common allele (0.59 vs. 0.36/year) and the association was present only in current and ex-smokers. There was a significant interaction between the amount smoked and rs16986718 genotypes (p = 0.014) and a positive correlation between the number of annual exacerbation episodes and amount smoked only in rs16986718G > A AA homozygotes. The prevalence of frequent exacerbators (≥2 exacerbation episodes/year) was 2.5 times higher in rs16986718G > A minor allele homozygotes than in common allele homozygotes (12.0% vs. 5.9%). Furthermore, the prevalence was 6 times higher in rs16986718G > A minor allele homozygotes who were current and ex-smokers than in nonsmokers (25.6% vs. 4.1%). The minor allele of rs16986718G > A in NLRP4 may be a genetic marker that predicts asthma exacerbation in adult asthmatics who smoke.

Effects of patient satisfaction and confidence on the success of treatment of combined rheumatic disease and interstitial lung disease in a multidisciplinary outpatient clinic.

OBJECTIVES: Multidisciplinary discussions (MDDs) have emphasized improve medical services and outcomes. We used a multidisciplinary approach to explore whether patient emotional satisfaction and confidence affected treatment outcomes in rheumatic disease (RD)-related interstitial lung disease (ILD). METHODS: From December 2015 to April 2017, we evaluated 23 patients with RD and ILD and 21 with idiopathic pulmonary fibrosis (IPF). Patients with RD and ILD were managed with MDDs. Patients with IPF received standardized medical care by the same pulmonologist. All patients completed brief multiple-choice questionnaires exploring their perceptions of their illnesses and their attitudes toward medical treatment, and completed the Patient Health Questionnaire-2. RESULTS: The MDD patients could more easily identify disease symptoms regardless of age stratification (under 65 age: P = 0.020, 65 years or older: P = 0.003). Among the 65 years or older group, it shows higher levels of illness perception in terms of disease timeline in the MDD group (P = 0.035). Also, the MDD group reported higher levels of satisfaction in terms of the explanations they received and their involvement in discussion, and greater satisfaction with medical staff. However, the groups did not differ significantly between treatment outcomes such as changes in forced vital capacity, the diffusion capacity of carbon monoxide, or changes in high-resolution computed tomography. CONCLUSIONS: MDDs afforded satisfactory management compared with standardized medical care. The MDD group felt better attention fromand satisfaction with medical staff, and had greater identification in their treatment. Further research engaging in MDDs with a comparable control group is required.

Comparison of CPI and GAP models in patients with idiopathic pulmonary fibrosis: a nationwide cohort study.

The clinical course of idiopathic pulmonary fibrosis (IPF) is difficult to predict, partly owing to its heterogeneity. Composite physiologic index (CPI) and gender-age-physiology (GAP) models are easy-to-use predictors of IPF progression. This study aimed to compare the predictive values of these two models. From 2003 to 2007, the Korean Interstitial Lung Disease (ILD) Study Group surveyed ILD patients using the 2002 ATS/ERS criteria. A total of 832 patients with IPF were enrolled in this study. CPI was calculated as follows: 91.0 - (0.65 × %DLCO) - [0.53 × %FVC + [0.34 × %FEV1. GAP stage was calculated based on gender (0-1 points), age (0-2 points), and two physiologic lung function parameters (0-5 points). The two models had similar significant predictive values for patients with IPF (p < 0.001). The area under the curve (AUC) was higher for CPI than GAP for prediction of 1-, 2-, and 3-year mortality in this study. The AUC was higher for surgically diagnosed IPF patients than for clinically diagnosed patients. However, neither CPI nor GAP yielded good predictions of outcomes; the AUC was approximately 0.61~0.65. Although both CPI and GAP stage are significantly useful predictors for IPF, they have limited capability to accurately predict outcomes.

Factors affecting treatment outcome in patients with idiopathic nonspecific interstitial pneumonia: a nationwide cohort study.

BACKGROUND: The effects of corticosteroid-based therapy in patients with idiopathic nonspecific interstitial pneumonia (iNSIP), and factors affecting treatment outcome, are not fully understood. We aimed to investigate the long-term treatment response and factors affecting the treatment outcome in iNSIP patients from a multi-center study in Korea. METHODS: The Korean interstitial lung disease (ILD) Study Group surveyed ILD patients from 2003 to 2007. Patients were divided into two groups to compare the treatment response: response group (forced vital capacity (FVC) improves ≥10% after 1 year) and non-response group (FVC <10%). Factors affecting treatment response were evaluated by multivariate logistic regression analysis. RESULTS: A total of 261 patients with iNSIP were enrolled, and 95 patients were followed-up for more than 1 year. Corticosteroid treatment was performed in 86 patients. The treatment group showed a significant improvement in lung function after 1-year: FVC, 10.0%; forced expiratory volume (FEV1), 9.8%; diffusing capacity of the lung for carbon monoxide (DLco), 8.4% (p < 0.001). Sero-negative anti-nuclear antibody (ANA) was significantly related with lung function improvement. Sero-positivity ANA was significantly lower in the response group (p = 0.013), compared to that in the non-response group. A shorter duration of respiratory symptoms at diagnosis was significantly associated with a good response to treatment (p = 0.018). CONCLUSION: Treatment with corticosteroids and/or immunosuppressants improved lung function in iNSIP patients, which was more pronounced in sero-negative ANA and shorter symptom duration patients. These findings suggest that early treatment should be considered in iNSIP patients, even in an early disease stage.

Clinical significance of cigarette smoking and dust exposure in pulmonary alveolar proteinosis: a Korean national survey.

BACKGROUND: This study aimed to investigate clinical characteristics of Korean PAP patients and to examine the potential risk factors of PAP. METHODS: We retrospectively reviewed medical records of 78 Korean PAP patients diagnosed between 1993 and 2014. Patients were classified into two groups according to the presence/absence of treatment (lavage). Clinical and laboratory features were compared between the two groups. RESULTS: Of the total 78 PAP patients, 60% were male and median age at diagnosis was 47.5 years. Fifty three percent were ever smokers (median 22 pack-years) and 48% had a history of dust exposure (metal 26.5%, stone or sand 20.6%, chemical or paint 17.7%, farming dust 14.7%, diesel 14.7%, textile 2.9%, and wood 2.9%). A history of cigarette smoking or dust exposure was present in 70.5% of the total PAP patients, with 23% having both of them. Patients who underwent lavage (n = 38) presented symptoms more frequently (38/38 [100%] vs. 24/40 [60%], P < 0.001) and had significantly lower PaO2 and DLCO with higher D(A-a)O2 at the onset of disease than those without lavage (n = 40) (P = 0.006, P < 0.001, and P = 0.036, respectively). Correspondingly, the distribution of disease severity score (DSS) differed significantly between the two groups (P = 0.001). Based on these, when the total patients were categorized according to DSS (low DSS [DSS 1-2] vs. high DSS [DSS 3-5]), smoking status differed significantly between the two groups with the proportion of current smokers significantly higher in the high DSS group (11/22 [50%] vs. 7/39 [17.9%], P = 0.008). Furthermore, current smokers had meaningfully higher DSS and serum CEA levels than non-current smokers (P = 0.011 and P = 0.031), whereas no difference was found between smokers and non-smokers. Regarding type of exposed dust, farming dust was significantly associated with more severe form of PAP (P = 0.004). CONCLUSION: A considerable proportion of PAP patients had a history of cigarette smoking and/or dust exposure, suggestive of their possible roles in the development of PAP. Active cigarette smoking at the onset of PAP is associated with the severity of PAP.

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

PURPOSE: Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. METHODS: A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. RESULTS: Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. CONCLUSIONS: Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two.

Incidence and Risk Factors of Pneumonia in Hospitalized Patients with Seasonal Influenza A or B.

BACKGROUND: Most patients with influenza recover spontaneously or following treatment with an anti-viral agent, but some patients experience pneumonia requiring hospitalization. We conducted a retrospective review to determine the incidence and risk factors of pneumonia in hospitalized patients with influenza A or B. METHODS: A total of 213 patients aged 18 years or older and hospitalized with influenza between January 2012 and January 2015 were included in this study. A reverse-transcriptase polymerase chain reaction assay was used to detect the influenza A or B virus in the patients' sputum samples. We collected demographic and laboratory data, combined coexisting diseases, and radiologic findings. RESULTS: The incidence of pneumonia was higher in patients in the influenza A group compared to those in the influenza B group (68.6% vs. 56.9%), but this difference was not statistically significant. The presence of underlying respiratory disease was significantly associated with pneumonia in the influenza A group (adjusted odds ratio [OR], 3.975; 95% confidence interval [CI], 1.312-12.043; p=0.015). In the influenza B group, the white blood cell count (adjusted OR, 1.413; 95% CI, 1.053-1.896; p=0.021), platelet count (adjusted OR, 0.988; 95% CI, 0.978-0.999; p=0.027), and existence of an underlying medical disease (adjusted OR, 15.858; 95% CI, 1.757-143.088; p=0.014) were all significantly associated with pneumonia in multivariate analyses. CONCLUSION: The incidence of pneumonia was 65.7% in hospitalized patients with influenza A or B. The risk factors of pneumonia differed in hospitalized patients with influenza A or B.

The activation of NLRP3-inflammsome by stimulation of diesel exhaust particles in lung tissues from emphysema model and RAW 264.7 cell line.

BACKGROUND/AIMS: Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome. In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation. METHODS: RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1ß (IL-1ß), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry. RESULTS: NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of IL-1ß in RAW 264.7 cells. The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC. CSE and DEPs increased the secretion of IL-1ß in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of IL-1ß by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: 309 ± 19 pg/mL vs. 151 ± 13 pg/mL, respectively, p < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, p < 0.05). NAC inhibited CSE- and DEP-induced IL-1ß secretion in both the normal and elastase-induced emphysema groups. NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC. CONCLUSIONS: The NLRP3-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.

Increased antioxidant activity after exposure of ozone in murine asthma model.

BACKGROUND: Ozone is well known as an important component of ambient air pollutants. Ozone can aggravate respiratory symptoms in patients with bronchial asthma, but, not in healthy person. We hypothesized asthma itself may show different response to ozone compared to nonasthma. OBJECTIVE: This study was performed to evaluate the differences of response to ozone between normal and asthmatic mice model in terms of status of oxidant injury and antioxidant activity. METHODS: Three parts per million of ozone was exposed to ovalbumin (OVA)-induced murine asthma model for 3 hours at 3, 7, 14, 21 days after completion of asthma model. Airway responsiveness to methacholine was measured after completion of asthma model. Bronchoalveolar lavage (BAL), protein extraction from lung for Western blot and immunohistochemistry of 4-hydroxy-2-nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), NF-E2 related factor 2 (Nrf-2), and activity of glutathione were performed at before and each ozone exposure day. RESULTS: Airway hyper-responsiveness and increased eosinophils in BAL fluid were observed in asthma model. In asthma model, the expression of 4-HNE already more increased at baseline (without ozone) compared to those in sham model. This increased expression is more enhanced at 3 days after ozone exposure. The expression of PCNA was significantly increased in OVA-model compared to those in sham model. The expression of Nrf-2 was observed at baseline, and 3 and 7 days after exposure ozone in asthma model, but not in sham model. The activity of glutathione increased significantly after exposure of ozone, but not in sham model. CONCLUSION: Murine asthma model has enhanced oxygen toxicity and antioxidant activity response to ozone.

Role of S100A9 in the development of neutrophilic inflammation in asthmatics and in a murine model.

S100A9 is an endogenous danger signal that promotes and exacerbates the neutrophilic inflammatory response. To investigate the role of S100A9 in neutrophilic asthma, S100A9 levels were measured in sputum from 101 steroid-naïve asthmatics using an ELISA kit and the levels were significantly correlated with percentages of neutrophils in sputum. Intranasal administration of recombinant S100A9 markedly increased neutrophil numbers at 8h and 24h later with concomitant elevation of IL-1ß, IL-17, and IFN-γ levels. Treatment with an anti-S100A9 antibody restored the increased numbers of neutrophils and the increased airway resistance in OVA/CFA mice toward the levels of sham-treated mice. Concomitantly, the S100A9 and neutrophil elastase double positive cells were markedly reduced with attenuation of IL-1ß, IL-17, and IFN-γ levels by the treatment with the anti-S100A9 antibody. Our data support a role of S100A9 to initiate and amplify the neutrophilic inflammation in asthma, possibly via inducing IL-1ß, IL-17 and IFN-γ.

Asthma-COPD Overlap Shows Favorable Clinical Outcomes Compared to Pure COPD in a Korean COPD Cohort.

PURPOSE: Comparisons of the characteristics of chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome (ACOS) have been the focus of several studies since the diseases were defined by the Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. However, no consensus is available yet. In this study, we aimed to compare the characteristics of asthma-COPD overlap (ACO) and COPD. METHODS: We retrospectively reviewed 1,504 patients with COPD in a Korean COPD Subtype Study cohort. The occurrence of ACO was defined as a positive response to a bronchodilator (an increase in forced expiratory volume in 1 second [FEV1] of 12% and 200 mL). RESULTS: Among 1,504 patients with COPD, 223 (14.8%) were diagnosed with ACO. Men (95.5%) and current smokers (32.9%) were more prevalent in the ACO group compared with the pure COPD group (90.5% and 25.3%, respectively; P=0.015 and P=0.026, respectively). Patients with ACO had a better quality of life (St. George's Respiratory Questionnaire for COPD score=31.0±18.0 [mean±standard deviation]) than those with pure COPD (35.3±19.1) (P=0.002). Although the prevalence of acute exacerbation was not different between the 2 groups, patients with severe exacerbation required hospital admission significantly more frequently in the pure COPD group than in the ACO group. Patients with ACO showed a higher likelihood of FEV1 recovery than those with pure COPD (P<0.001). CONCLUSIONS: We suggest that ACO is characterized by less severe symptoms, and therefore it might lead to rare severe exacerbation and the possibility of lung function recovery.